Transfectants were shown to be inducible with 10-7 M Cd++ without toxic effect. In the presence of inducer, all clones not only express high levels of TGF- α mRNA but also produce and secrete high levels of (8-10 fold) biologically active TGF- α which can successfully compete with EGF for binding to EGF-R. After induction only one clone (LH1) had increased cloning in soft agar two fold above that in non-induced controls. High levels of TGF- α produced by the clones had little or no impact on EGF-R mRNA transcription. LNCaP had low levels (3-4x104) of EGF-R binding sites/cell. Transfectants showed less/no binding sites prior to suramin (1 mg/ml) stripping of receptors from the high levels of TGF- α produced by them. But, after the suramin treatment low levels (2-3x104) of EGF-R sites/cell can be recovered.

Thus, TGF- α produced by the clones down regulates the RGF-R in an autocrine fashion and promotes a differential growth response tightly coupled to the level of occupancy of EGF-R in serum free media. Keywords :